Genes involved in the determination and differentiation of adult tissues in Drosophila melanogaster have been identified by genetic interactions with homeotic and segmentation genes already known to be required in these tissues. Many new genes required for transcriptional activation of developmental genes have been identified. One of these new genes, brahma, encodes a large nuclear protein conserved from yeast to man. brahma mutations have in turn been used to identify other interacting genes required for transcriptional activation. The osa gene, which shows allele-specific interactions with brahma mutations, has been cloned by transposon tagging. The allele-specific interactions between brahma and osa suggests that the proteins interact directly in transcriptional activation. Genetic interactions with brahma have also been identified for the trithorax, ash1, and kohtalo genes. The RNA polymerase II transcription factor TFIID is a complex of at least eight proteins. Chromosomal deficiencies that remove the genes encoding the 60 and 110 kDa polypeptides of TFIID have been identified. To isolate mutants for these two proteins, over ninety essential mutations have been generated in each chromosomal region. These mutations represent an average of four mutations per gene in each region. The wild-type genes have been reintroduced into transgenic strains by P-element-mediated transformation to determine which mutations affect the 60 and 110 kDa polypeptides. Only one gene required for post-transcriptional regulation of homeotic genes has been identified. This is the kismet gene. kismet encodes a family of novel nuclear proteins, only one of which appears to be essential. The association of kismet proteins with specific sites on polytene chromosomes suggests that kismet may interact with the homeotic proteins in regulating their target genes.